Low affinity Fc receptors, immune regulation and disease.

The body’s own antibody-tagging system can sometimes turn against it, and this project homes in on two molecular switches that control that dangerous shift. These switches—receptors called FcgammaRIIb and FcgammaRIIIb—sit on immune cells and interpret signals from antibodies. When they malfunction, the immune system can attack healthy tissue, causing autoimmune diseases such as lupus or vasculitis. The researchers recently discovered that one of these receptors is essential for the long-term survival of antibody-producing plasma cells, a finding that opens a direct link to how the body loses tolerance to itself. They will now use mouse models and human genetic studies to map exactly how these receptors drive autoimmunity and influence susceptibility to infections like pneumonia and malaria. If successful, this work could reveal new drug targets for autoimmune diseases—conditions that affect millions and are often treated with blunt immunosuppressants. The team is already testing ways to deliberately activate or block each receptor, aiming to design therapies that restore immune balance without shutting down the entire system. This is fundamental science with a clear translational horizon: understanding the molecular levers of immune regulation could eventually lead to treatments that are far more precise than current options.